Terpenes and sterols manifest a variety of biological functions and activities as hormones, plant regulatory substances, pheromones, antibiotics, and phytoalexins among others. A knowledge of the stereospecificity and mechanisms associated with individual steps in the biosynthetic pathways to them will facilitate the rational design of specific inhibitors or promoters. The objectives of this research are to elucidate the sterochemistry and mechanisms of important reactions involved in terpene and sterol biosynthesis by labelling experiments, by synthesis of potential intermediates, and by investigations with model compounds. Another goal is the synthesis and evaluation of potential inhibitors of key enzymes on the biosynthetic pathways. The specific aims may be summarized as follows: 1. Synthesis of 9,10-syn diterpenes and investigation of the sterochemistry of the cyclizations leading to them as part of the biosynthetic pathway to the momilactone phytoalexins. 2. Stereoselective total synthesis of the cyclobutyl isomer of presqualene as a new intermediate in, or inhibitor or, squalene biosynthesis. 3. Synthesis and evaluation of aza analogs of carbocation intermediates as novel branch-point inhibitors. 4. Elucidation of the complete stereochemistry of the prenylation reaction forming the cis double bonds of dolichol and rubber by means of stereospecific tritium labelling. 5. Synthesis and investigation of bridged phosphates and pyrophosphates as precursors to bidentate carbocation-phosphate ion pairs or as transition inhibitors of mono-and diterpene cyclases. 6. Determination of the stereochemistry and isotope effects of eliminations that terminate enzymatic cyclizations producing enantiomeric monoterpenes.